Yonsei Med J.  2019 Mar;60(3):277-284. 10.3349/ymj.2019.60.3.277.

Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation

• Lee SR
• Lee YS
• Park JS
• Cha MJ
• Kim TH
• Park J
• Park JK
• Lee JM
• Kang KW
• Shim J
• Uhm JS
• Kim J
• Kim C
• Kim JB
• Park HW
• Joung B
• Choi EK

• KMID: 2441305
• DOI: http://doi.org/10.3349/ymj.2019.60.3.277

Abstract

PURPOSE
Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs.
MATERIALS AND METHODS
In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations.
RESULTS
We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHAâ‚‚DSâ‚‚-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use.
CONCLUSION
In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.

Keyword

Atrial fibrillation; non-vitamin K antagonist oral anticoagulant; drug labeling; dose

MeSH Terms

Anticoagulants*
Asian Continental Ancestry Group*
Atrial Fibrillation*
Body Weight
Cohort Studies*
Drug and Narcotic Control
Drug Labeling
Female
Hemorrhage
Humans
Hypertension
Korea
Male
Off-Label Use
Prescriptions
Prospective Studies*
Risk Factors
Rivaroxaban
Stroke
Anticoagulants
Rivaroxaban

Figure

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  Fig. 1 Differences in drug-specific dose reduction recommendations for each NOAC and discrepancies in NOAC dosing. NOAC, non-vitamin K antagonist oral anticoagulant.

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  Fig. 2 Label adherence for NOAC dosing in the study population. NOAC, non-vitamin K antagonist oral anticoagulant.

• 

  Fig. 3 Factors associated with off-label underdosing. CrCl, creatinine clearance; TE, thromboembolic events; TIA, transient ischemic attack; CI, confidence interval.

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